Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide)

Synaptogenic Peptide · Cognitive Enhancement

Overview

Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.

Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.

Improvements in spatial, working, and consolidation demonstrated across animal models.

Enhanced acquisition through increased synaptic plasticity.

Restoration in impairment models including scopolamine-induced amnesia.

Reduced amyloid burden in Alzheimer's models.

Mechanism

Improvements in spatial, working, and consolidation demonstrated across animal models.

Research areas

Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.
Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.
Improvements in spatial, working, and consolidation demonstrated across animal models.
Enhanced acquisition through increased synaptic plasticity.
Restoration in impairment models including scopolamine-induced amnesia.
Reduced amyloid burden in Alzheimer's models.
Decreased neuroinflammation and glial activation.
Protection of synapses in neurodegeneration models.
3-fold increase in dendritic spine formation demonstrated.
Increases brain-derived neurotrophic factor expression.
Promotes new blood vessel formation in brain.

Research notes

Headaches (most frequent side effect)
Anxiety or overstimulation
Sleep disruption when dosed late in day
Mental clarity increase
Severe or persistent headaches
Increasing anxiety or panic attacks
Significant mood changes or depression
Sleep disturbance beyond 3 days
Concerning neurological symptoms
Signs of overstimulation or mania
Injection site reactions (if injectable)
Not FDA approved - research compound only
Theoretical cancer risk via c-Met activation
Cancer history (avoid due to c-Met pathway)
Pregnancy or breastfeeding
No long-term human safety data
Yes, headaches are the most common side effect reported with Dihexa use, particularly during initial doses. Anxiety, overstimulation, and sleep disruption can also occur due to its potent neuroplastic effects. Starting at low doses (5mg) and timing away from bedtime may minimize these effects.

References

FAQs

How much more potent is Dihexa than BDNF for synapse formation?

Dihexa is approximately 10 million times more potent than BDNF at promoting synaptogenesis. This extraordinary potency comes from its picomolar binding affinity for HGF (Kd = 65 pM) and activation of c-Met receptor, enabling profound cognitive effects at very low doses compared to other peptides.

What's the difference between Dihexa and its prodrug Fosgonimeton?

Fosgonimeton is a prodrug form of Dihexa designed for better pharmacokinetics and clinical development. It showed efficacy in Phase I trials for Alzheimer's disease with normalization of P300 latency. Fosgonimeton may be more stable and bioavailable than raw Dihexa, though research is ongoing.

Is Dihexa safe to combine with other cognitive-enhancing peptides?

Combining Dihexa with other potent nootropics like Semax or Selank may cause overstimulation or excessive neuroplasticity. Limited human data exists for combinations. If stacking, start conservatively and monitor for increased headaches, anxiety, or mood disturbances indicating neural overstimulation.